Iron Deficiency More Common in Preterm Infants Not Fed with Breast Milk

A new retrospective cohort study found iron deficiency was significantly more prevalent among non-breast-milk-fed very premature infants (<31 weeks gestational age) at 4–6 months corrected age (CA), despite a higher iron intake than breast-milk-fed infants.¹

Preterm infants are at an increased risk for developing iron deficiency and it is recommended to provide them with prophylactic iron supplementation. However, guidelines from professional associations such as the American Academy of Pediatrics (AAP) only make general recommendations on iron requirements in preterm infants and do not specify the between those fed with iron-rich formula and those who are breast milk-fed.²

“These observations suggest the need to revisit international recommendations for iron supplementation in these infants,” wrote the investigative team led by Satvinder Ghotra, MD, MSc, faculty of medicine at Dalhousie University.¹

Citing the lack of literature on iron status in very premature infants fed with breast milk versus formula, the investigative team had previously infants who were exclusively formula-fed had a higher likelihood of iron deficiency.³ However, their findings were unclear if the identified association was due to lower iron intake in the formula feeding group or a result of decreased iron bioavailability from the formula.

The objective of the current population-based study was to further explore the relationship between feeding type and iron deficiency among very premature infants born in Nova Scotia, Canada between 2005 and 2018.¹ Iron supplements (2–3 mg/kg/day) were started at 2–4 weeks chronologic age, according to Canadian Pediatric Society (CPS) guidelines.⁴ Those born ≥1000 g were started on 2–3 mg/kg/day of iron while infants born <1000 g received 3–4 mg/kg/day of iron.¹

For formula-fed infants, investigators took the iron obtained from formula into consideration when deciding additional iron dosage. Hemoglobin and serum ferritin levels were also measured every 3–4 weeks during the neonatal stay and iron dosages were adjusted as needed, to a maximum of 6 mg/kg/day. Overall, iron deficiency was categorized as serum ferritin <20 µg/L or <12 µg/L at 4- and 6-months, respectively.

According to feeding type at 4–6 months CA, infants were divided into breast-milk-fed and non-breast-milk-fed cohorts. Among 917 very premature infants born during the study period, 570 met study inclusion criteria and 392 were included after exclusions due to lack of data or loss of follow-up. Of these 392 infants, 107 were exclusively or partially breast milk-fed, and 285 were exclusively fed with iron-rich formula.

Infants in the non-breast-milk-fed cohort had higher mean daily formula intake and received more iron from formula than breast-milk-fed infants. However, a higher percentage of breast milk-fed infants were taking supplements (79.4% vs. 57.9%) and received more iron on average from supplements. Upon analysis, the total daily iron intake was greater in the non-breast-milk-fed cohort, with a combination of formula and supplements (2.6 mg/kg/day vs. 2.0 mg/kg/day in the breast-milk-fed cohort).

Despite these data, investigators found a greater percentage of non-breast-milk-fed infants were iron deficient (36.8% vs. 20.6%; odds ratio [OR], 2.25). Clinical characteristics of the cohorts showed the non-breast-milk-fed group had a lower mean maternal age and a greater prevalence of smoking and single-parent status. After adjusting for these maternal and neonatal variables, non-breast-milk-fed infants remained at a higher risk of iron deficiency (OR, 2.11 [95% CI, 1.24 - 3.59]; P = .01).

“Further research on the bioavailability of iron from formula versus from breast milk to corroborate these findings is important,” Ghotra and colleagues wrote. “Addition of more bioavailable iron species to formulas should be considered over increasing the iron content of formulas in order to prevent iron deficiency in formula-fed very premature infants.”

References

1. _{Power G, Morrison L, Kulkarni K, et al. Non Breast-Milk-Fed Very Preterm Infants Are at Increased Risk of Iron Deficiency at 4-6-Months Corrected Age: A Retrospective Population-Based Cohort Study. Nutrients. 2024;16(3):407. Published 2024 Jan 30. doi:10.3390/nu16030407}
2. _{Baker, R.D.; Greer, F.R.; Committee on Nutrition. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0–3 years of age). Pediatrics 2010, 126, 1040–1050}
3. _{Landry, C.; Dorling, J.; Kulkarni, K.; Campbell-Yeo, M.; Morrison, L.; Ledwidge, J.; Vincer, M.; Ghotra, S. Postdischarge Iron Status in Very Preterm Infants Receiving Prophylactic Iron Supplementation after Birth. J. Pediatr. 2022, 247, 74–80.e2}
4. _{Canadian Medical Association. Nutrient needs and feeding of premature infants. Nutrition Committee, Canadian Paediatric Society. CMAJ 1995, 152, 1765–1785}